Abstract
Atherosclerosis and nephrosclerosis have been described in captive and wild howlers.5,7 This report describes the occurrence of glomerular atherosclerosis and nephrosclerosis in five black howlers (Alouatta caraya), three red howlers (Alouatta seniculus sara) and one golden howler (Alouatta seniculus straminea) from two zoological facilities in the United States. Table 1 summarizes the signalment and history for each animal. Two were males and seven were females. Age at necropsy ranged from 5–26 years, and average age was 16.1 years. Five animals died and four were humanely euthanatized. The most common reported historic findings included chronic renal failure (three animals), protein-losing nephropathy (two animals), weight loss (three animals), depression or lethargy (three animals) and constipation (two animals). Serum chemistries were available for seven monkeys and abnormal values included azotemia (seven animals), elevated serum creatinine (seven animals), hypoalbuminemia(seven animals), hypoproteinemia (six animals), hypercholesterolemia (five animals), and hyperphosphatemia (five animals). Urinalyses were available for four monkeys and abnormal values included proteinuria (three animals), hematuria (three animals), and glucosuria (three animals).
Table 1. Signalment and history for howler monkeys with glomerular disease
Case
|
Species
|
Age (year)
|
Sexa
|
Clinical presentation
|
Blood chemistry values
|
Urinalysis
|
Disposition
|
1
|
Black
|
11
|
M
|
Protein-losing nephropathy
|
Azotemia Hyperphosphatemia Elevated creatinine Hypercholesterolemia Hypoproteinemia Hypoalbuminemia
|
Proteinuria Hematuria (trace)
|
Euthanatized
|
2
|
Black
|
19
|
F
|
Protein-losing nephropathy Weight loss Vomiting
|
Azotemia Hyperphosphatemia Elevated creatinine Hypercholesterolemia Hypoproteinemia Hypoalbuminemia Hyperglycemiab
|
Proteinuria Hematuria (trace) Glucosuriab
|
Died
|
3
|
Golden
|
18
|
F
|
Chronic renal failure Weight loss Constipation Pica
|
Azotemia Hyperphosphatemia Elevated creatinine Hypercholesterolemia Hypoproteinemia Hypoalbuminemia
|
Proteinuria Glucosuria
|
Died
|
4
|
Red
|
5
|
F
|
Found recumbent and hypothermic
|
NAc
|
NA
|
Died
|
5
|
Red
|
16
|
F
|
Hospitalized for intensive care No further history
|
Azotemia Hyperphosphatemia Elevated creatinine Hypercholesterolemia Hypoproteinemia Hypoalbuminemia
|
NA
|
Died
|
6
|
Black
|
19
|
F
|
Lethargy and pulmonary congestion Cardiomegaly
|
Azotemia Hyperphosphatemia Elevated creatinine Hypoalbuminemia Neutrophilic leukocytosis w/left shift Mild anemia
|
NA
|
Euthanatized
|
7
|
Red
|
9
|
F
|
No history
|
Azotemia Elevated creatinine Hypoproteinemia Hypoalbuminemia Hypercholesterolemia Regenerative anemia
|
NA
|
Died
|
8
|
Black
|
22
|
F
|
Lethargy Emaciation Kyphosis Anemia Chronic renal failure
|
Azotemiad Elevated creatinine Hypoproteinemia Hypoalbuminemia Mild anemia
|
Hematuria
|
Euthanatized
|
9
|
Black
|
26
|
M
|
Anorexia Depression Constipation Kyphosis Spondylosis Chronic renal failure
|
NA
|
Hematuria Proteinuria
|
Euthanatized
|
aM=male; F=female.
bAnimal was on fluid therapy at time urinalysis was obtained.
cNot available.
dMost recent bloodwork was 5 months prior to death.
Table 2 summarizes the gross and histologic findings for each animal. The most common gross findings were small, shrunken or scarred kidneys (seven animals), globoid or hypertrophic heart (four animals), thoracic or pleural effusions (four animals), aortic or valvular plaques (two animals), endocardiosis (two animals) and yellow fat (two animals). Histologically, all animals had varying and generally severe glomerular and renal vascular atherosclerosis, membranoproliferative and mesangioproliferative glomerulopathy, renal tubular protein casts, nephrosclerosis, and chronic interstitial nephritis. Extra-renal arteriosclerosis and atherosclerosis were detected in seven animals, especially in the heart and aorta. Eight animals had varying degrees of myocardial fibrosis. Some additional histologic findings included chronic enteritis or enterocolitis (six animals), pancreatic acinar cell atrophy (four animals), hemosiderosis in lymph nodes gut or liver (three animals), atrophy of fat (three animals), islet cell hyperplasia (two animals), and hyperplastic goiter (two animals).
Table 2. Gross and histologic lesions associated with glomerular disease in howler monkeys
Case
|
Gross findings
|
Renal histologic lesions
|
Other histologic lesions
|
1
|
Small kidneys Yellow fat Thick left ventricle
|
Atherosclerosis MPGa Sclerosis CINb Protein casts
|
Goiter Atrophy of fat Pancreatic fibrosis and atrophy Arteriosclerosis/atherosclerosis (heart valve) Chronic colitis
|
2
|
Pale granular kidneys Plaque on pulmonary valve
|
Atherosclerosis MPG Sclerosis CIN
|
Goiter Myocardial fibrosis Hemosiderosis Arteriosclerosis/atherosclerosis (ovary, vagina, aorta, kidney) Pheochromocytoma Chronic colitis
|
3
|
Small pale kidneys Globoid heart with thick left ventricle Thickened uterus
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Mycobacteriosis Hemosiderosis Myocardial fibrosis Atherosclerosis/arteriosclerosis (heart) Chronic colitis
|
4
|
Small pale pitted kidneys Hypertrophic left ventricle
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Myocardial fibrosis Myocardial infarction Pancreatic acinar degeneration and fibrosis Thyroid hypoplasia and fatty infiltration Chronic enterocolitis
|
5
|
Generalized edema Ascites Hydrothorax Diarrhea Scarred kidneys
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Atherosclerosis (heart, stomach) Myocardial fibrosis Islet hyperplasia Atrophy of fat Chronic enteritis
|
6
|
Obesity Pulmonary consolidation Enlarged left atrium Ascites Hydrothorax
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Florid pulmonary edema Myocardial fibrosis Pancreatic acinar atrophy
|
7
|
Thin pale mucous membranes Yellow fat Hydrothorax Aortic aneurism Left ventricular hypertrophy Endocardiosis
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Atherosclerosis/arteriosclerosis (aorta, spleen, urinary bladder, uterus, ovary, colon, pancreas) Aortic aneurism Myocardial fibrosis
|
8
|
Emaciation Endocardiosis Aortic plaques Gastric ulcers Pale foci in kidneys
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Atherosclerosis (mesentery, lymph node, spleen, aorta, ovary) Myocardial fibrosis Endocardiosis and arteriosclerosis Gastric mineralization Atrophy of fat Acinar atrophy and islet hyperplasia
|
9
|
Ascites Saponified fat Small pale kidneys Constipation
|
Atherosclerosis MPG Sclerosis CIN Protein casts
|
Atherosclerosis/arteriosclerosis (heart, spleen, intestine) Chronic enteritis myocardial fibrosis Hemosiderosis
|
aMembranoproliferative glomerulonephritis.
bChronic interstitial nephritis.
The renal lesions in these howlers were attributed to atherosclerosis, hypertension, ischemia, and aging. Glomerular protein leakage and tubular protein casts were attributed to glomerular atherosclerosis and glomerulosclerosis. The nephrosclerosis and chronic interstitial nephritis were attributed to tubular abrogation associated with protein casts as well as ischemic change associated with hypertension and atherosclerosis. The presentations in these animals are similar to various nephropathies described in humans that are associated with acquired derangements in lipid metabolism, atherosclerosis, diabetes mellitus, and hypertension.2-4,8-10 High circulating levels of low-density lipoproteins, glomerular-free radical injury, and ischemia are believed to play important roles in the development of chronic renal disease in humans.2-4,8-10 Chronic renal disease with protein losing nephropathy and atherosclerosis appear to be over-represented in captive howler monkeys fed diets that may not be considered atherogenic in other species, indicating that these animals may be exquisitely sensitive to the affects of hypercholesterolemia, atherosclerosis, and associated development of renal disease.1,5-7,11 Strict dietary management and periodic monitoring of serum cholesterol levels may be indicated for howler monkeys.
Literature Cited
1. Chamberlain, J., G. Nelson, K. Milton. 1993. Fatty acid profiles of major food sources of howler monkeys (Alouatta palliata) in the neotropics. Experientia. 15:820–24.
2. Galle, J., K. Heermeier. 1999. Atherogenic lipoproteins, oxidative stress, and cell death. Kidney Int. Suppl. 71:S62–65.
3. Gin, H., V. Rigalleau, M. Aparicio. 2000. Lipids, protein intake, and diabetic nephropathy. Diabetes Metab. 4:45–53.
4. Makanjuola, A.D., M. Suresh, P. Laboi, P.A. Kalra, J.E. Scoble. 1999. Proteinuria in atherosclerotic renovascular disease. QJM. 92: 515–18.
5. Malinow, M.R., C.A. Maruffo. 1965. Aortic atherosclerosis in free-ranging howler monkeys (Alouatta caraya). Nature. 206:948–949.
6. Malinow, M.R., C.A. Maruffo. 1966. Naturally occurring atherosclerosis in howler monkeys (Alouatta caraya). J. Atheroscler. Res. 6:368–380.
7. Malinow M.R., C.A. Storvick. 1968. Spontaneous coronary lesions in howler monkeys (Alouatta caraya). J. Atheroscler. Res. 8:421–431.
8. Moorhead J.F., C. Brunton, R.L. Femando, A. Bums, Z. Varghese. 1996. Do glomerular atherosclerosis and lipidmediated tubulo-interstitial disease cause progressive renal failure in man? Blood Purif. 14:58–66.
9. Moorhead, J.F., C. Brunton, Z. Varghese. 1997. Glomerular atherosclerosis. Miner Electrolyte Metab. 23:2387–90.
10. Rodriguez-Porcel, M., J.D. Krier, A. Lerman, P.F. Sheedy, J.C. Romero, C. Napoli, L.O. Lerman. 2001. Combination of hypercholesterolemia and hypertension augments renal function abnormalities. Hypertension. 37:774–80.
11. Vie, J.C., B. Moreau, B. de Thoisy, P. Fournier, C. Gentry. 1998. Hematology and serum biochemistry values of free-ranging red howler monkeys (Alouatta seniculus) from French Guiana. J. Zoo Wildl. Med. 29:142–149.